The on-again, off-again beef between the 2 is firmly back on, after Floyd shared a message on social media that began with ... "Curtis 'Confidential Informant' Jackson, you're mad because your oldest son Marquees mother doesn’t want to be with you! Your Son, your own flesh and blood don't want nothing to do with you!"

And Mayweather was just getting started.

Floyd goes on to blast 50 for stealing his style from Ja Rule, gossiping "like a bitch" and filing for bankruptcy .. and accuses him of being a fake gangster and a "certified snitch" (and claims he has proof).

There's more -- a lot more -- so check it out.

It's unclear what exactly sparked this outburst, but there a couple of possibilities. The rapper recently poked fun at the boxer for being illiterate (again) ... and the 2 have had some issues over 50 being sued by Teairra Mari.

Either way, this could get even uglier ... stay tuned.

3:15 PM PT -- That didn't take long -- 50 responded by sharing a photo of Floyd with tears in his eyes ... and bringing up his domestic violence cases.